Mast cells attach to connective tissue components following aggregation of high affinity receptors for IgE (FcepsilonRI) or low-affinity receptors for IgG (FcgammaRII/III) on the membrane surface. This process is mediated by integrins. FcR induced adhesion is transient and occurs through "inside-out signaling". Signaling through FcR that leads to adhesion requires participation of the gamma chain. Mast cells spontaneously adhere to vitronectin. This event is followed by the phosphorylation of intracellular proteins including focal adhesion kinase (FAK). FAK is also phosphorylated after aggregation of FcepsilonRI, or after the addition of c-kit liqand, also termed stem cell factor (SCF). The autophosphorylation activity of FAK is also increased when mast cells are activated by SCF, by adhesion to vitronectin, or following FcepsilonRI aggregation. IL-3 dependent mast cells undergo apoptosis following removal of IL-3. This is prevented by the addition of SCF. Addition of TGF-beta prevents this SCF-mediated rescue, but does not effect IL-3-dependent proliferation. Mast cell apoptosis is accompanied by down-regulation of Bcl-2. Mouse bone marrow-derived mast cells respond to both IL-3 and c-kit ligand and are inhibited by m-CSF, GM-CSF, and gamma-IFN. Mouse peripheral blood mononuclear cell-derived mast cells respond only to c- kit ligand. Human bone marrow-derived or peripheral blood-derived human mast cells may be cultured from a CD34+ FcepsilonRI cell population in the presence of SCF. CD34 positivity is rapidly lost in culture, while the cell population becomes FcepsilonRI+. Mast cell outgrowth is inhibited by IFN- gamma, but not IFN-alpha2b, and this inhibitory effect is not abrogated by IL-4.